Huang S H, Pittler S J, Huang X, Oliveira L, Berson E L, Dryja T P
Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School, Boston, Massachusetts, USA.
Nat Genet. 1995 Dec;11(4):468-71. doi: 10.1038/ng1295-468.
Retinitis pigmentosa (RP) constitutes a group of genetically heterogeneous progressive photoreceptor degenerations leading to blindness and affecting 50,000-100,000 people in the U.S. alone. Over 20 different RP loci have been mapped, of which six have been identified. Three of these encode members of the rod photoreceptor visual transduction cascade: rhodopsin, the rod cGMP-gated cation channel alpha subunit, and the beta subunit of cGMP-phosphodiesterase (PDEB). As null mutations in PDEB cause some cases of RP and since both alpha and beta subunits are required for full phosphodiesterase activity, we examined the gene encoding the alpha subunit of cGMP phosphodiesterase (PDEA) in 340 unrelated patients with RP. We found three point mutations in PDEA in affected members of two pedigrees with recessive RP. Each mutation alters an essential functional domain of the encoded protein and likely disrupts its catalytic function. PDEA is the seventh RP gene identified, highlighting the extensive genetic heterogeneity of the disorder and encouraging further investigation into the role of other members of the phototransduction cascade in RP.
视网膜色素变性（RP）是一组具有遗传异质性的进行性光感受器退行性病变，可导致失明，仅在美国就影响着5万至10万人。已定位了20多个不同的RP基因座，其中6个已被确定。其中3个编码视杆光感受器视觉转导级联反应的成员：视紫红质、视杆cGMP门控阳离子通道α亚基和cGMP磷酸二酯酶（PDEB）的β亚基。由于PDEB中的无效突变会导致某些RP病例，并且由于α和β亚基都是完全磷酸二酯酶活性所必需的，我们在340名无亲缘关系的RP患者中检测了编码cGMP磷酸二酯酶α亚基（PDEA）的基因。我们在两个患有隐性RP的家系的患病成员中发现了PDEA的三个点突变。每个突变都改变了编码蛋白的一个重要功能域，并可能破坏其催化功能。PDEA是第七个被鉴定的RP基因，突出了该疾病广泛的遗传异质性，并鼓励进一步研究光转导级联反应的其他成员在RP中的作用。
